Transdermal administration is easy and convenient as compared with oral administration and administration by injection, and may also be advantageous in terms of duration of the effect and reduction of expression of the side effects, whereby that is an excellent administration method. However, in order to permeate the active ingredient into the body by transdermal administration, the active ingredient is to be penetrated through the skin which constitutes the primary barrier of the living body and, therefore, its bioavailability (amount of the drug absorbed with a blood flow) is inherently low. Accordingly, in order to achieve the improvement of bioavailability of active ingredients, it has been conducted that dipropylene glycol, hexylene glycol, isoparaffin, sodium laurylsulfate, an ethylene oxide adduct of lauryl alcohol, polyethylene glycol fatty acid ester, polyoxyethylene sorbitan fatty acid ester, propyl carbonate, sodium pyrrolidonecarboxylate, urea, lactic acid, sodium lactate, lecithin, dimethyl sulfoxide, pyrrolidonecarboxylate, nicotinate, N-methylproline ester, cholesteryl oleate, amine oxide or the like is compounded with preparations for external application as a transdermal absorption enhancer.
Up to now, the present inventors have energetically carried out research and development for transdermal absorption of active ingredients and, as a result, they have found that, when retinoic acid having an action of enhancing regeneration of the skin by enhancing differentiation and growth of keratinocytes is included into capsules of a nanometer level (nano-particles) followed by applying to the skin surface, retinoic acid is able to be transdermally absorbed in efficient and sustained-releasing manner without compounding of the transdermal absorption enhancers as mentioned above (Non-Patent Document 1 and Non-Patent Document 2).
Non-Patent Document 1: Yoko Yamaguchi, “Novel Nano-Technology for Transdermal Delivery”, Bio Venture, vol. 4, no. 6, pages 62 to 64, 2004
Non-Patent Document 2: Y. Yamaguchi, T. Nagasawa, N. Nakamura, M. Takenaga, M. Mizoguchi, S. Kawai, Y. Mizushima and R. Igarashi, “Successful Treatment of Photo-Damaged Skin of Nano-Scale atRA Particles Using a Novel Transdermal Delivery”, 104, 29 to 40, 2005.